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Aggressors Need Dopamine, and Victims Require Serotnin

07.12.2004

The Novosibirsk researchers have managed to establish connection between mice’s aggressive behavior, biochemical modifications in their brain and the genes that cause those modifications.

Aggressive behavior is to a large extent genetically determined. The evidence of that are experiments with laboratory animals, including their successful selection into high- and low-aggressive lines. However, the “aggression gene” as such will hardly be ever found. Nevertheless, the researchers have managed to find the genes that are connected with aggressive behavior. Thus, researchers of the Institute of Cytology and Genetics (Siberian Branch, Russian Academy of Sciences) and Novosibirsk Institute of Bioorganic Chemistry (Siberian Branch, Russian Academy of Sciences, Novosibirsk) have analyzed biochemical modifications taking place in the brain of mice after aggressive collisions and have found the genes responsible for that.

Male mice scuffled with each other every day: the stronger ones used to attack and assault, the weaker ones – used to run away or posed as the subordinated. As a result of recurring fights some males won victories all the time and gained “experience of victors” - they became even more aggressive. Others got into position of “ chronical victims” who are in the state of constant stress. Both types changed their behavior. However, as the researchers have demonstrated, biochemistry of brain changed as well. The researchers measured the content of basic neuromediators – i.e. the substances that transmit a signal from one nerve cell to another – in the brain of winner mice and victim mice, and the products of their chemical transformations. The researchers were most interested in the dopamine and serotonin neuromediators. It has turned out that the recurring aggression experience of the “winners” leads to activation of the neurons system that uses dopamine (i.e., the dopaminergic system). However, the recurring experience of defeats with the “victims” causes weakening the dopaminergic system work, but in return, it activates the system of neurons that use serotonin – the serotonergic system. Apparently, these two systems work in antiphase.

At the next phase of investigation, the researchers faced the task of passing “from behavior to the gene”. Proceeding from biochemical results, the researchers worked with the genes that are connected with the dopaminergic and serotonergic systems of the brain. The difficulty is that neuromediators are not proteins. A gene contains information about protein synthesis. However, there exist multiple proteins that ensure the work of neuromediators, for example, enzymes participating in their transformations, and protein receptors on the membrane. The genes of these proteins constituted the subject of investigation. Namely, COMP gene that encodes enzyme of the dopamine and noradrenaline metabolism, TG gene that limits the rate of synthesis of these neuromediators, DAT gene that ceases the dopamine action on the cellular membrane, SERT gene that provides for transfer of serotonin and MAOA that causes its inactivation. The work of all these genes changed to the opposite with the winners and victims. The researchers made sure that formation of aggressive or submissive (subordinated) type of behavior causes realignment of work of several genes which leads to changes in activity of the neuromediator systems. Thus, the researchers have managed to find experimental approach that allows to establish connection between behavior to the gene. At least in terms of aggression. The research has been funded through grants from the Russian Foundation for Basic Research and INTAS.

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